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Biology subjects

Encinas, J. M.

Publications and source records attributed to Encinas, J. M..

6 recordsLinked to original sources

Evolutionary convergence of sensory circuits in the pallium of amniotes

The amniote pallium contains sensory circuits structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. Our study employs birthdating analysis, single-cell RNA and spatial transcriptomics, and mathematical modeling to compare the development and evolution of known pallial circuits across birds (chick), lizards (gecko) and mammals (mouse). We reveal that neurons within these circuits stations are generated at varying developmental times and brain regions across species, and found an early developmental divergence in the transcriptomic progression of glutamatergic neurons. Together, we show divergent developmental and evolutionary trajectories in the pallial cell types of sauropsids and mammals. Our research highlights significant differences in circuit construction rules among species and pallial regions. Interestingly, despite these developmental distinctions, the sensory circuits in birds and mammals appear functionally similar, which suggest the convergence of high-order sensory processing across amniote lineages.

developmental biology↗

Traumatic brain injury enhances the intrinsic excitation and excitatory transmission of granule cells

Traumatic brain injury (TBI) leads to a wide range of long-lasting physical and cognitive impairments. Changes in neuronal excitability and synaptic functions in the hippocampus have been proposed to underlie cognitive alterations. The dentate gyrus (DG) acts as a "gatekeeper" of hippocampal information processing and as a filter of excessive or aberrant input activity. In this study, we investigated the effects of controlled cortical impact, a model of TBI, on the excitability of granule cells (GCs) and excitatory postsynaptic transmission in the DG at three time points, 3 days, 15 days and 4 months after the injury. Our results indicate that changes in the short term are related to intrinsic properties, while changes in the long term are more related to input and synaptic activity, in agreement with the notion that TBI-related pathology courses with an acute phase and a later long-term secondary phase. A biphasic response, a reduction in the shorter term and an increase in the long term, was found in TBI neurons in the frequency of sEPSC. These changes correlated with a loss of complexity in the pattern of the synaptic input, an alteration that could therefore play a role in the chronic and recurrent TBI-asssociated hyperexcitation.

neuroscience↗

BirthSeq, a new method to isolate and analyze dated cells from any tissue in vertebrates

Embryonic development is a complex and dynamic process that unfolds over time and involves the production of increasing numbers of cells, as well as the diversification of different cell types. The impact of developmental time on the formation of the central nervous system is well-documented, with evidence showing that time plays a critical role in establishing the identity of neuronal subtypes. However, the study of how time translates into genetic instructions driving cell fate is limited by the scarcity of suitable experimental tools. We introduce BirthSeq, a new method for isolating and analyzing cells based on their birth date. This innovative technique allows for in vivo labeling of cells, isolation via FACS, and analysis using high-throughput techniques. We demonstrate the effectiveness of BirthSeq for single-cell RNA sequencing and novel spatially resolved transcriptomic approaches in brain development across three vertebrate species (mouse, chick, and gecko). Overall, BirthSeq provides a versatile tool for studying any tissue in any vertebrate organism, helping to fill the necessity in developmental biology research by targeting cells and their temporal cues. SUMMARY STATEMENTBirthSeq allows the isolation and investigation of alive cells according to their birthdate, in any kind of tissue and vertebrate species.

developmental biology↗

Traumatic brain injury modifies adult hippocampal neural stem cell fate to promote neurogenesis at the cost of astrogliogenesis.

Moderate Traumatic brain injury (TBI) can result in long-lasting changes in brain function. Although frequently spared from the acute primary injury, the hippocampus becomes affected during a secondary phase that takes place hours, or even days, after TBI, contributing to cognitive deficits. The hippocampus is one of the few brain areas in the adult brain harboring native neural stem cells (NSCs) that continue to generate new neurons (neurogenesis), and to a lesser extent new astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, very little is known about how TBI may affect hippocampal astrogliogenesis. Here, we aimed to assess how TBI affects hippocampal NSCs and their subsequent commitment to the neuronal or astroglial lineages. Using a controlled cortical impact model of TBI, single cell RNA sequencing and spatial transcriptomics, we observed a cell population-specific increase in NSC-derived neuronal cells and a decrease in NSC-derived astrocytic cells. These cellular changes were associated with cell-population specific changes in gene expression and dysplasia within the dentate gyrus. Overall, our findings support the conclusion that TBI modifies adult hippocampal NSC fate to promote neurogenesis at the cost of astrogliogenesis, and highlights specific cell populations as possible targets to counteract the changes induced by TBI in the hippocampus.

neuroscience↗

Generation of adult hippocampal neural stem cells occurs in the early postnatal dentate gyrus and depends on cyclin D2

In the hippocampus, lifelong neurogenesis is maintained by a pool of multipotent adult neural stem cells (aNSCs) residing in the subgranular zone of the dentate gyrus (DG). Yet, the mechanisms guiding the transition of NSCs from developmental to adult remain unclear. By using nestin-reporter mice deficient for D2, a cyclin expressed mainly postnatally, we show that the aNSC pool is established through D2-dependent proliferation during the first two weeks of life. The absence of D2 allows the normal development of the DG until birth but prevents the postnatal formation of radial glia-like aNSCs. Additionally, retroviral fate mapping demonstrates that aNSCs are born on-site from precursors located in the DG shortly after birth. Altogether, our data suggest that aNSCs are a population distinct from developmental NSCs and thus imply that adult hippocampal neurogenesis is not a mere continuation of development.

neuroscience↗

Human Dental Pulp Stem Cells Grown In Neurogenic Media Differentiate Into Endothelial Cells And Promote Neovasculogenesis In The Mouse Brain.

Dental Pulp Stem Cells (DPSCs) have a demonstrated capacity to acquire neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult DPSCs cultured in Neurocult media (Stem Cell Technologies), a cell culture medium without serum routinely used for the expansion of adult neural stem cells (NSCs). Our results showed for the first time, that non-genetically modified adult DPSCs cultured with Neurocult generated neurosphere-like dentospheres expressing the NSC markers Nestin and GFAP, but also the vascular endothelial cell marker CD31. One month post-intracranial graft into athymic nude mice, human CD31+ or Nestin+ DPSC-derived cells were found tightly associated with brain blood vessels increasing their laminin staining. These results suggest that DPSCs integrated and contributed to an increased generation of neovasculature within brain tissue and that Neurocult medium constituted a fast and efficient way to obtain endothelial cells from human DPSCs.

bioengineering↗